Abstract

Background:Serum concentration of cartilage oligomeric matrix protein (COMP) is related to the degree of cartilage destruction in patients with rheumatoid arthritis (RA) and shows a mechanosensitive response to ambulatory loads. We showed previously, that individuals with positive for anti-citrullinated protein antibody (ACPA+) status already show bone loss. It is unclear if these individuals experience cartilage deterioration and how this is related to physical activity.Objectives:To test whether soluble COMP levels in ACPA+ display the same response as RA patients after a walking exercise and explore the association between overall serum COMP levels and physical activity.Methods:RA patients and ACPA+ individuals (IRACE cohort: Individuals at Risk for Arthritis Cohort Erlangen; Ethics approval 334_16B) were enrolled in the study after written informed consent. Inclusion criteria were age between 18 and 69 years, RA (by 2010 ACR/EULAR criteria) or ACPA+ (without clinical manifestation of RA and prior treatment with glucocorticoids, DMARDs and biologics). The study comprised three visits (baseline (Visit 1), 6 (Visit 2), and 12 months (Visit 3). During each visit, serum samples were collected after 30 minutes rest (pre) and at 0, 30, 60, and 120 minutes after a 30-minute walking exercise. Serum COMP concentration was analyzed by commercial ELISA. Physical activity duration (hours) was measured using an activity monitor for 7 consecutive days, and physical activity level (metabolic equivalent of the task (MET)) was quantified using the International Physical Activity Questionnaire (IPAQ). The reponse of COMP levels to the walking exercise was modelled using linear mixed-effects regression models. The association between physical activity and overall serum COMP concentrations was analyzed using a mixed-effects regression model (Random effects: individuals, visits and COMP measurement time points).Results:28 RA and 22 ACPA+ patients participated in this prospective study. Table 1 summarizes patient demographics and outcome measures. Serum COMP levels increased in response to the walking exercise in both groups but the acute response was not different in RA patients compared to ACPA+ individuals. Higher physical activity level by IPAQ was associated with higher overall COMP concentration. Doubling of total physical activity is associated with an increase in serum concentration of 0.32 U/L (95%CI 0.09 to 0.54, p=0.006). ACPA+ individuals but not RA patients show an association between serum COMP concentration and physical activity duration (Figure 1).Table 1.Summary of subject characteristics and outcome measures.DescriptivesMeasureACPA+RAindividuals, number (%)22 (44.0)28 (56.0)Age, years (mean (SD))47.6 (12.8)57.0 (9.1)Female, number (%)14 (28.0)19 (38.0)BMI, kg/m2, mean (SD)25.1 (5.6)27.2 (5.8)Anti-CCP positive (N)1714DAS28-score, mean (SD)2.5 (1.2)2.7 (1.4)Cartilage Oligomeric Matrix Protein (U/l)Visit 1Visit 2Visit 3ACPA+RAACPA+RAACPA+RApre-walking exercise9.4 (2.8)9.7 (3.8)10.8 (2.2)11.3 (4.5)10.2 (2.5)10.5 (3.9)09.5 (2.6)10.4 (3.9)11.8 (1.8)12.2 (4.0)10.1 (2.0)11.1 (4.6)309.2 (2.2)9.9 (3.6)10.8 (1.9)11.4 (4.4)9.2 (2.2)10.6 (4.2)609.2 (2.0)9.4 (4.0)10.4 (2.1)10.9 (4.5)8.6 (2.9)10.0 (4.0)1209.2 (2.1)9.5 (4.0)9.6 (1.8)10.9 (4.4)8.0 (2.4)9.9 (3.9)Figure 1.Estimated marginal mean COMP by physical activity duration for RA and ACPA+.Conclusion:Pre-exercise serum COMP concentration is similar in ACPA+ and RA and shows a similar increase in response to walking in both groups. Physical activity duration appears to influence serum COMP concentration in ACPA+. Given that acute COMP release was not different between ACPA+ and RA while overall COMP values are associated with physical activity level, the discrepancy between ACPA+ and RA for this association can be explained by reduced vigor or qualitative differences in physical activity.Disclosure of Interests:Lisa Bleckwedel-Rolack: None declared, Koray Tascilar: None declared, Veronika Nees: None declared, Julia Hühne: None declared, Axel Hueber: None declared, Jürgen Rech Speakers bureau: Abbvie, Biogen, BMS, Chugai, GSK, Lilly, MSD; Mylan, Novartis, Roche, Sanofi, Sobi, UCB, Consultant of: Abbvie, Biogen, BMS, Chugai, GSK, Lilly, MSD; Mylan, Novartis, Roche, Sanofi, Sobi, UCB, Grant/research support from: Novartis, Sobi, Georg Schett Speakers bureau: Lilly, Novartis, Consultant of: Lilly, Novartis, Gilead, BMS, Abbvie, Grant/research support from: Lilly, Novartis, Arnd Kleyer Speakers bureau: Lilly, Novartis, Consultant of: Lilly, Novartis, Gilead, BMS, Abbvie, Grant/research support from: Lilly, Novartis, Anna-Maria Liphardt Speakers bureau: Mylan, Paid instructor for: Abbvie, Consultant of: MEDA Pharma, Grant/research support from: Novartis

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